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Blood, 15 October 2001, Vol. 98, No. 8, pp. 2403-2411
HEMATOPOIESIS
Molecular pathways in bone marrow homing: dominant role of
 4 1 over 2-integrins
and selectins
Thalia Papayannopoulou,
Gregory V. Priestley,
Betty Nakamoto,
Vivian Zafiropoulos, and
Linda M. Scott
From the University of Washington, Seattle.
The specific retention of intravenously administered hemopoietic
cells within bone marrow is a complex multistep process. Despite recent
insights, the molecular mechanics governing this process remain largely
undefined. This study explored the influence of
 2-integrins on the homing to bone marrow and
repopulation kinetics of progenitor cells. Both antifunctional
antibodies and genetically deficient cells were used. In addition,
triple selectin-deficient mice were used as recipients of either
deficient (selectin or 2) or normal cells in homing
experiments. The homing patterns of either 2 null or
selectin null cells into normal or selectin-deficient recipients were
similar to those of normal cells given to normal recipients.
Furthermore, spleen colony-forming units and the early bone marrow
repopulating activity for the first 2 weeks after transplantation were
not significantly different from those of control cells. These data are
in contrast to the importance of 2-integrin and
selectins in the adhesion/migration cascade of mature leukocytes. The
special bone marrow flow hemodynamics may account for these
differences. Although early deaths after transplantation can be seen in
recipients deficient in CD18 and selectin, these are attributed to
septic complications rather than homing defects. However, when
2- or selectin-null donor cells are treated with anti- 4 antibodies before their transplantation to normal
or selectin-deficient recipients, a dramatic inhibition of homing
(>90%) was found. The data suggest that the
41/vascular cell adhesion molecule-1 pathway alone is capable of providing effective capture of cells within
the bone marrow, but if its function is compromised, the synergistic
contribution of other pathways, that is, 2-integrins or
selectins, is uncovered.
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